A novel cyclic signaling in the dermis in animal models has been identified that coordinates stem cell activity and regulates 1) ___ in large populations of hairs. The signaling switch involves the bone morphogenetic protein (Bmp) pathway. Conceptually, the findings have important implications for stem cell research and in understanding how stem cell activity is regulated during regeneration. The research presents a new dimension for the regulation of hair regrowth and ultimately 2) ___ regeneration. The hair is an important model for organ regeneration in 3) ___ because it is one of the few organs that regenerates regularly. Recent work in the field has established hair cycling as one of the mainstream models for organ regeneration. However, most of these works focus on the cyclic regeneration of one single hair 4) ___. Each of us has thousands of hair follicles. In this study, the coordinative behavior of cyclic regeneration in a population of organs, was analyzed. The research team found that hairs, even in normal mice, regenerate in waves, rather than 5) ___. The findings suggest that hair stem cells are regulated not only by the micro-environment within one hair follicle — as has previously been thought — but also by adjacent hair follicles, other skin compartments and systemic hormones, in a 6) ___ order. At the 7) ___ level, the findings showed that periodic expression of Bmp in the skin macro-environment appears to be at the center of the mechanism for coordinated hair stem cell activation. When many hairs regenerate, they must communicate activation signals among themselves. At different time points the macro-environment can be either permissive or suppressive for stem cell 8) ___.This research shows that the formation of new tissues or organs from stem cells — such as the formation of new hairs — can be more robust if it occurs in a permissive macro-environment. It is hoped that this research will draw more attention to the hair follicle as the model for physiological regeneration in mammals, and as an abundant source of adult stem cells for the purposes of stem cell therapy. The work also has critical implications for research using the mouse skin as a model for tumor growth or drug delivery. Many studies assume the mouse skin is a homogeneous and stable environment for testing, but variations in results have been obtained. Understanding the unexpected dynamics of the living mouse skin will help future experimental designs” (see January 17, 2008 issue of Nature).

ANSWERS: 1) regeneration; 2) organ; 3) mammals; 4) follicle; 5) individually; 6) hierarchical; 7) molecular; 8) activation